Palladium-Catalyzed Enantioselective

Carboiodination of Olefin-Tethered Aryl Iodides

Literature Report 3

Reporter

Checker

Date

: Xiang Li

: Zi-Biao Zhao

: 2019-07-08

Zhang, Z.-M.; Zhang, J. et al. J. Am. Chem. Soc. 2019, 141, 8110.

Contents

2

1

2

Introduction

3

Pd-Catalyzed Asymmetric Carboiodination

Summary

CV of Prof. Junliang Zhang

3

Research:

Conjugated enynes, small ring chemistry, asymmetric catalysis

Education:

1993-1997 B.A., Tianjin University

1997-2002 Ph.D., SIOC

2002-2003 Research assistant, SIOC

2003-2005 Postdoc, University of Cologne

2005-2006 Postdoc, The University of Chicago

2006-2017 Professor, East China Normal University

2017-Present Professor, Fudan University

Introduction

4

Introduction

5

Pd-Catalyzed C-I Bond Formation

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a) C(sp2)−I Bond Formation

b) C(sp3)−I Bond Formation

C(sp2)−I Bond Formation

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Yu, J.-Q. et al. Angew. Chem. Int. Ed. 2008, 47, 5215.

C(sp2)−I Bond Formation

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Yu, J.-Q. et al. Angew. Chem. Int. Ed. 2008, 47, 5215.

C(sp2)−I Bond Formation

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Yu, J.-Q. et al. Org. Lett. 2010, 12, 3140.

Yu, J.-Q. et al. Angew. Chem. Int. Ed. 2008, 47, 6452.

C(sp2)−I Bond Formation

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Yu, J.-Q. et al. J. Am. Chem. Soc. 2013, 135, 16344.

C(sp2)−I Bond Formation

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Yu, J.-Q. et al. Science 2014, 346, 451.

Colobert, F. et al. Angew. Chem. Int. Ed. 2014, 53, 13871.

C(sp2)−I Bond Formation

12

Colobert, F. et al. Angew. Chem. Int. Ed. 2014, 53, 13871.

C(sp3)−I Bond Formation

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Lautens, M. et al. J. Am. Chem. Soc. 2011, 133, 1778.

C(sp3)−I Bond Formation

14

Lautens, M. et al. J. Am. Chem. Soc. 2011, 133, 1778.

C(sp3)−I Bond Formation

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Tong, X. et al. J. Am. Chem. Soc. 2011, 133, 6187.

Lautens, M. et al. Angew. Chem. Int. Ed. 2012, 51, 9870.

C(sp3)−I Bond Formation

16

Lautens, M. et al. Angew. Chem. Int. Ed. 2012, 51, 9870.

C(sp3)−I Bond Formation

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Lautens, M. et al. J. Am. Chem. Soc. 2011, 133, 14916.

C(sp3)−I Bond Formation

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Lautens, M. et al. Angew. Chem. Int. Ed. 2014, 53, 7908.

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Zhang, J. et al. J. Am. Chem. Soc. 2019, 141, 8110.

Pd-Catalyzed Asymmetric Carboiodination

Effect of Reaction Parameters

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Entry Variation from the standard conditions Conv. (%)a Yield (%)b Er (%)c

1 none 100 80d 95.5:4.5

2 L1 instead of L3 <5 trace -

3 L2 instead of L3 - - -

4 L4 instead of L3 - - -

5 no K2CO3 73 58 95:5

6 Cs2CO3 instead of K2CO3 74 14 92.5:7.5

7 Pd(OAc)2 instead of Pd2(dba)3•CHCl3 82 41 91.5:8.5

8 PhMe instead of iPr2O 100 78 94.5:5.5

Reaction conditions: 1a (0.1 mmol), 10 mol% of catalyst ([Pd] to L = 1:2), solvent (2 mL), 100 oC, 14 h. a

Determined by NMR. b NMR yield. c Determined by HPLC for product. d 0.3 mmol of 1a, isolated yield.

Substrate Scope

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Substrate Scope

Substrate Scope

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Substrate Scope

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The Reaction Mechanism

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Summary

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Zhang, J. et al. J. Am. Chem. Soc. 2019, 141, 8110.

The First Paragraph

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From various natural product and bioactive molecules to materials, and

clean energy, organic halides undoubtedly represent versatile synthetic

precursors even directly as target molecules. Over past decades, transition-

metal catalyzed synthesis of racemic organic halides has attracted

tremendous attention. Notably, Lautens disclosed a perfect atom

economical strategy to construct 2,3-dihydrobenzofuran bearing an alkyl

iodide group by a domino sequence involving the oxidative addition of aryl

iodide, alkene insertion and C(sp3)-I reductive elimination from a Pd(II)

intermediate. A particular focus was on the rate-determing reductive

elimination step, which needs an exceptionally bulky and electron rich

phosphine ligand such as QPhos or P(tBu)3 facilitated the C(sp3)-I reductive

elimination by limiting the formation of tetracoordinated intermediates.

The First Paragraph

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By the employment of excess electron-rich bisphosphine ligand DPPF,

Tong realized an elegant example of Pd(0)-catalyzed carboiodination

reaction of (Z)-1-iodo-1,6-diene. The Ni-catalyzed intramolecular

carboiodination reaction was also realized to generate valuable halogenated

3,3-disubstituted heterocycles and a moderately enantioselective process

has also been reported. Despite much elegant progress in the racemic or

diastereoselective synthesis has been made, the development of transition-

metal (especially palladium-catalyzed) asymmetric carboiodination reaction

with high effciency remains extremely challenging, besides the

enantioselectivity, “there are few ligands known to promote the key reductive

elimination” mentioned by Lautens. Thus, the development of the highly

efficient and enantioselective transition-metal catalyzed carboiodination is

desired.

The Last Paragraph

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In summary, we have developed the first highly enantioselective

palladium-catalyzed carboiodination of unactivated alkenes with the use of

N-Me-Xu3 as the chiral ligand and K2CO3 as the additive, which provides

an efficient synthesis of chiral 3,3-disubstituted 2,3-dihydrobenzofuran,

indolines and chromane bearing an alkyl iodide and one all-carbon

quaternary stereocenter. The mechanism of this Pd(0)-catalyzed

asymmetric carboiodination of alkenes has been investigated with density

functional theory. The DFT calculations indicated that the alkene insertion

rather than the reductive elimination is the rate-determining step and

accounts for the enantioselectivity and high reactivity. Moreover, further

direction will focus on the development of asymmetric domino

carbopalladation-initiated reactions and will be reported in the due course.

Acknowledgement

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